PROJECT /SUMMARY ABSTRACT My prior training and exposures linked with my long-term goal makes this K43 Emerging Global Award for Developing Countries the ideal opportunity for me to realise my aspiration as an independent researcher in the field of translational genomics in non-communicable diseases. Genetic research in the area of NCDs in general, but particularly in diabetes is very sparse in Africa. I was however opportuned to be part of the only notable diabetes genetic project in West Africa, the Africa America Diabetes Mellitus Study, by which the seed of my interest in genetic research was cultivated. Recently, through the NIH D43 collaborative research-training programme between University of Ibadan and University of Chicago, I was exposed further to the impact of genomics advances in improving diagnostic precision of diabetes. In order to advance my career as independent investigator, I now ask whether acquisition of competency in diagnostic molecular genomics in NCDs, and its application in the clinic setting, can translate into improved diagnostic precision of diabetes, particularly detection of monogenic cause of diabetes as a test case. Non-communicable diseases (NCDs) such as diabetes have devastating consequences on African nations such as Nigeria. Contributing to this is very little access to genetic testing resulting in misdiagnosis or, in some cases like monogenic diabetes (MD), non-diagnosis. Consequently, the proportion, spectrum and pattern of undiagnosed MD among patients with commoner types of diabetes in Nigeria remain unknown. It is not known whether identifying and addressing physicians' related barriers to genetic testing could facilitate genotypic description of MD in Nigeria, as a prototype for application of genetic testing to other NCDs. My overall objective for this K43 application is to describe the frequency and spectrum of genetic variants of MD in Nigeria, while I obtain training and competency in diagnostic molecular genomics focused on NCDs, so as to improve diagnostic precision of these conditions and thereby make Ibadan, Nigeria, a referral center for the entire West Africa. My hypothesis is that physicians' related factors constitute significant barriers to application and utility of genetic testing in the clinic, with consequent undiagnosed or misdiagnosed MD among patients with diabetes in Nigerian, who are likely to have different genotypic variants compared to other population. In the research plan, I describe the three specific aims that need to be achieved in the Nigerian setting to move from non-application of genetic testing in the clinic to using the outcome of genetic testing to describe the genotypic spectrum of a previously undiagnosed condition such as MD in Nigeria. The knowledge and experience gained can then be extended to other NCDs and, through training of others, increase capacity and impact the whole of West Africa. First, there is need to identify physicians' related barriers by carrying out surveys among eligible doctors practicing in public health institutions in Ibadan. Secondly, I plan to develop and implement a genomics programme to diagnose and classify diabetes in the clinic through design of a practical, contextualised decision support tool for physicians. Lastly, using a two-step strategy of screening likely patients by a practical guideline and sequencing DNA of selected patients, I will then describe the frequency, spectrum and genotypic pattern of MD among clinic patients with diabetes. In order to be successful at application of genomics to improve diagnostic precision of NCDs in Nigeria, I need further training in genomics, bioinformatics as well as leadership skills required to build a RCE in a LMIC. I have identified and assembled a mentorship committee in these areas and together we have planned a curriculum of courses training programme that will lead me to this end. The K43 award will enable me to develop the competency to independently carry out phenotype-genotype matching in NCDs, and make Ibadan a referral and training centre for other parts of West Africa.